Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation.
Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation.
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DOI：
10.1016/j.neurobiolaging.2013.04.016
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发表时间：
2013-10
影响因子：
4.2
通讯作者：
Lazarov O
中科院分区：
文献类型：
--
作者：
Demars MP;Hollands C;Zhao Kda T;Lazarov O
神经发生被认为在认知功能和海马可塑性中起作用。以前的研究表明，神经发生随着年龄的增长而下降。然而，神经发生下降的发病和机制尚未完全阐明。在这里，我们表明，主要的下降发生在成年期，在衰老之前。神经发生的下降发生在齿状回的颗粒下层和脑室下区，主要是由于快速增殖的神经祖细胞数量减少。重要的是，这种下降可以通过脑室内注射重组可溶性淀粉样前体蛋白（sAPPα）来挽救，该蛋白调节成人大脑中的神经祖细胞增殖。对应物sAPPβ是APP的淀粉样蛋白生成裂解途径的产物，在与sAPPα等摩尔浓度下，在体外和体内均未表现出增殖作用。这些观察结果表明，成年期是上调神经发生（如提高sAPPα水平）的干预措施的适当时间窗口，以预防大脑可塑性和认知功能下降。
Neurogenesis is thought to play a role in cognitive function and hippocampal plasticity. Previous studies suggest that neurogenesis declines with aging. However, the onset and mechanism of declined neurogenesis are not fully elucidated. Here we show that the major decline in neurogenesis takes place during adulthood, prior to aging. Decline in neurogenesis takes place in both the subgranular layer of the dentate gyrus and in the subventricular zone, and is primarily due to reduced number of fast-proliferating neural progenitor cells. Importantly, this decline can be rescued by intraventricular injection of recombinant soluble amyloid precursor protein (sAPPα) that regulates neural progenitor cell proliferation in the adult brain. The counterpart sAPPβ, a product of the amyloidogenic cleavage pathway of APP, fails to exhibit a proliferative effect in vitro and in vivo, in equimolar concentration to sAPPα. These observations suggest that adulthood is an appropriate time window for an intervention that upregulates neurogenesis, such as enhancement of sAPPα levels, for the prevention of declining brain plasticity and cognitive function.
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影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
DOI：
10.1002/0470870834.ch14
发表时间：
2000-01-01
期刊：
NEURAL TRANSPLANTATION IN NEURODEGENERATIVE DISEASE: CURRENT STATUS AND NEW DIRECTIONS
影响因子：
--
作者：
Kempermann, G;Gage, FH
通讯作者：
Gage, FH
影响因子：
23.9
作者：
Encinas, Juan M.;Michurina, Tatyana V.;Peunova, Natalia;Park, June-Hee;Tordo, Julie;Peterson, Daniel A.;Fishell, Gord;Koulakov, Alex;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
5.3
作者：
Enwere, E;Shingo, T;Weiss, S
通讯作者：
Weiss, S
影响因子：
4.8
作者：
Belyaev, Nikolai D.;Kellett, Katherine A. B.;Turner, Anthony J.
通讯作者：
Turner, Anthony J.